Cardiac output computer

ABSTRACT

A method and apparatus for determining the rate of flow of a substance such as blood in a closed circulatory system whereby a detectable indicator substance is injected into the blood upstream of the heart and the density of that substance in the blood downstream measured and integrated in time to determine the flow of blood pumped through the heart in volume units per time. Distortion of the density waveform by recirculation and consequent error in the calculated flow rate is avoided by detecting two points on the exponential decay from the density peak and extrapolating the integral of the remainder of the wave form from these points. In contrast to prior art techniques, an analogue signal reflecting the integral of the waveform is produced and employed to obtain the flow of blood through the heart.

United States Patent Czekajewski [451 Mar. 21, 1972.

[54] CARDIAC OUTPUT COMPUTER [22] Filed: Jan. 26, 1970 [21] App1.No.:5,888

[52] U.S. Cl. ..235/183, 128/205 F, 128/2.1 R, 235/92 FL, 328/142,328/165 [51] Int. Cl ..G06g 7/18, A61b 5/02 [58] Field ofSearch..235/183,92 FL;328/l27;

Shubin et al.: Automated Measurement of Cardiac Output in DIV/DEEPatients by use of a Digital Computer from: Medical & Biol. Engineeringpp. 353- 360 1967 Primary Examiner-Malcolm A. Morrison AssistantExaminer-Felix D. Gruber Attorney-Cushman, Darby & Cushman 57] ABSTRACTA method and apparatus for determining the rate of flow of a substancesuch as blood in a closed circulatory system whereby a detectableindicator substance is injected into the blood upstream of the heart andthe density of that substance in the blood downstream measured andintegrated in time to determine the flow of blood pumped through theheart in volume units per time. Distortion of the density waveform byrecirculation and consequent error in the calculated flow rate isavoided by detecting two points on the exponential decay from thedensity peak and extrapolating the integral of the remainder of the waveform from these points. In contrast to prior art techniques, an analoguesignal reflecting the integral of the waveform is produced and employedto obtain the flow of blood through the heart.

18 Claims, 4 Drawing Figures 0/ VIPER PATENTEUMARZI I972 SHEET 3 BF 3CARDIAC OUTPUT COMPUTER BRIEF DESCRIPTION OF THE PRIOR ART AND SUMMARYOF THE INVENTION The invention relates to a method and apparatus fordetermining the rate of flow of blood or a similar liquid in a closedcirculatory system by the injection of an indicator upstream of theheart and measuring and integrating the density of the injectordownstream to determine the rate of flow.

For proper detection and treatment of many cardiac disorders it isnecessary to accurately ascertain the rate atwhich the heart is pumpingblood through the circulatory system. One simple and widely usedtechnique for accomplishing this result is to inject a suitableindicator upstream of the heart and to measure the density of theindicator in the blood downstream. When the indicator mixessubstantially uniformly with the blood and when the indicator isinjected rapidly enough, the relation between the flow rate V in volumeper unit of time and the amount of the injected indicator is roughlydetermined by the formula:

j qdt qdt=the integral of the measured indicator .2

density in time. Any indicator which may be properly injected anddetected can be used and these include radioactive material, dye, hot orcold saline solutions, etc. For a detailed discussion of the use ofindicator techniques see Symposium on Use of Indicator-Dilution Technicsin a Study of Circulation Circulation Research, Vol. 10, No. 3, Part 2,March,

Moreover, the typical curve for the detected indicator density after theindicator is injected upstream and-measured downstream increasesrelatively quickly in time to a peak value and then decays substantiallyexponentially to zero. However, in a closed circulatory system such asthe human body, at some point during the exponential tail, the indicatorfluid, which has already passed the detecting point and been detected,begins returning past the detecting point after a complete journeythrough the circulatory system and is redetected. When this occurs, thedensity curve is distorted and the tail of the curve loses itsexponential character and the curve measured displays a second peakvalue which is, of course, substantially lower in amplitude than thefirst.

Because recirculation thus destroys a portion of the curve which is usedto determine the flow rate, it is normally necessary to predict thedistorted portion of the exponential tail from the undistorted portionand to determine the integral of that curve from the undistorted and thepredicted portions. Since the most accurate portion of the exponentialtail of the dilution curve normally occurs between 80 and 50 percent ofthe peak value, it is desirable to use points within this range toconstruct the portion of the theoretical exponential tail destroyed byrecirculation. As discussed in greater detail below, it is well knownand can be easily shown that the integral of an exponentially decayingcurve is equal to the initial amplitude of the curve times a value 1-where -r is the time required for the curve to decay to I/e of itsinitial value. Accordingly, by selecting some point high on theexponential tail of the density waveform and integrating that valueuntil the waveform has decayed to He of that value, an integral which istheoretically identical to the integral of the waveform which isactually destroyed by recirculation is produced.

However, according to one aspect of the invention, it has beendiscovered that recirculation may even cloud results somewhat which areproduced according to the above approach. As discussed in greater detailbelow, this problem can be overcome by integrating for only a portion,such as half, of the time necessary for the waveform to decay to the 1/2level and then multiplying the resulting value before adding it to theintegral for the remainder of the density waveform.

In the Lehmann et al. US. Pat. No. 3,304,413, a similar arrangement fordetermining the flow rate of blood pumped through the heart by theinjection of an indicator upstream and the subsequent detection andintegration of the density of the indicator downstream of the heart isdisclosed. In this arrangement, a densiometer is employed to producedigital signals which are eventually applied to a counter and stored soas to produce a final indication of the integral of the densitywaveform. However such digital signals are unsatisfactory in thattheyare not signals which can be easily displayed and read and which can besimply employed with other signals to produce a displayed informationsignal which yields directly the flow rate.

According to another aspect of the present invention, the density curveis employed to produce analog signals. Further, in one embodiment of theinvention described below, the apparatus is designed to detect andindicate radical errors due to the mistake of personnel or the faults ofperipheral equipment. Provision is also made for calibrating theapparatus.

Many other objects and purposes of the invention will become clear fromthe following detailed description of the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a typical density curvefor an indicator injected upstream of the heart and detected downstreamof the heart.

FIG. 2 shows a density curve as in FIG. 1 wherein the remainder of thecurve from the point B can be simulated by integrating the value B forthe time 1' or integrating the value B for time 1/2 and doubling thatresult.

FIG. 3 shows in block diagram the invention of this application whereinthe density signal is applied to an analogue circuit to produce anoutput reflecting the rate of flow of the blood or other liquid.

FIG. 4 shows a block diagram of another embodiment of the invention.

DETAILED DESCRIPTION OF THE DRAWINGS Reference is now made to FIG. 1which shows an ideal curve for the density of an indicator such as dye,warm or cold saline solution, radioactive isotope, etc. which has beeninjected rapidly into the circulatory system upstream of the heart andwhich has passed through the heart and been detected by a conventionaldensiometer downstream to produce the waveform shown. As discussedbriefly above, the normal density waveform rises fairly steeply in timeto a peak labeled A and then decays substantially exponentially towardzero. However, as discussed above, in a closed circulatory system, suchas the human body, at some point during the exponential tail, indicatorfluid which has already been detected returns past the detecting pointand is once again detected to produce a second peak which, if employedto calculate the flow rate, will distort the flow rate determined fromthe curve.

Referring to FIG. 2, an approach is shown whereby this distortionresulting from recirculation can be eliminated by extrapolating theremaining distorted portion of the exponential curve from its relativelyundistorted position. Referring to FIG. 1, the integral of theexponentially decaying tail from the level B to the theoretical zerovalue is:

This mathematical operation suggests that the area under theexponentially decaying curve can be simulated by a rectangle having aheight equal to the amplitude of the exponentially decaying curve at itspoint of initiation and a width equal to the time constant 1. Moreover,it should be apparent that the time constant 1- is equal to the timewhich it takes the density waveform to decay from the level B to I/e ofits value or roughly 0.36788 B. Accordingly, by detecting the point Bhigh on the exponential tail, similarly detecting a point C equal to0.36788 B and integrating at the constant level B between these twopoints, an expression which is theoretically equivalent to the remainderof the exponentially decaying waveform is produced. This expression whenadded to the integral of the remainder of the waveform produces a signalwhich can be operated on to produce a number equal to the flow rate inwhatever units are desired.

Moreover, as discussed briefly above, it has been noted that by the timethat the waveform decays to l/e of some convenient level B, substantialdistortion exists. It has been discovered, however, that this distortioncan be substantially eliminated by integrating the value B, not for sometime r, but for some fraction of r, such as 7/2, and then multiplyingthe resultant value accordingly before adding it to the remainder of theintegrated waveform. In the example illustrated in FIG. 2, the interval-r/2 is employed and the integration of B for time r/2 is then doubledto produce an expression which is theoretically equivalent to theremainder of the exponential tail.

Reference is now made to FIG. 3 which shows a block diagram of theinvention of this application for producing an analogue output signaland preferably displaying the rate of blood flow through the heart, orof any other liquid through a closed circulatory system. As shown inFIG. 3, an electrical signal from a suitable densiometer with a signalamplitude varying with the density of the indicator detected is appliedto the input of the device and first passes to a conventional peak andhold circuit which follows the curve as it rises rapidly to the peaklevel A and retains peak level A after the curve begins to exponentiallydecay. Peak hold circuit 20 passes its output, which, after the waveformbegins to decay from peak A, remains at the level A, to conventionallevel or voltage dividers 22 and 24.

Level divider 22 is manually or automatically set to divide its input,which, during the exponential tail, is the peak level A, by a factor Kso as to generate an output signal level roughly equal to the level B,which is the level chosen to be integrated for the time 1- or a portionof the time 1' to simulate the remainder of the exponential tail. Leveldivider 24 likewise divides its input which during the tail is the peakvalue A by a second factor K to generate the level C, which is thepredetermined point on the exponentially decaying curve at whichintegration of the value B is to cease. As'should be apparent from thediscussion below, the separation in time between the levels B and C willbe the time interval 7 or a desired fraction thereof.

The output of level divider 22 is passed to a conventional comparatorcircuit 26 which also receives the initial input signal applied to peakhold circuit 20. Comparator circuit 26 is designed so that a suitableoutput signal, such as a pulse, is generated on output line 28 wheneverboth inputs to circuit 26 are at substantially the same level. Thus, asignal on line 28 is produced at the time the exponentially decayingwaveform applied to circuit 20 and circuit 26 reaches level B.Similarly, comparator circuit 30 receives both an input from leveldivider 24 and the original waveform applied to circuit 20 so that, likecomparator circuit 26, comparator circuit 30 generates a signal on itsoutput line 40 whenever its two inputs have the same level. Thus anoutput, such as a pulse, on line 40 results at the time the decayingwaveform reaches the level C.

The input signal to circuit 20, which represents the density of theindicator detected downstream of the heart, is also passed via line 42to a switching circuit 44 which normally holds its controlled switch 45in the illustrated position so that the input density waveform-normallypasses through switch 45 and the normally closed controlled switch 46 ofswitching circuit 47 to a conventional integrator 50. Integrator 50 thusintegrates in time the density waveform as it rises toward the peakvalue A and as it begins to decay exponentially.

When comparator circuit 26 produces its output signal on line 28, thatsignal is transmitted to switching circuit 44 which responds byimmediately shifting the position of its controlled switch 45 from theillustrated position and into connection with line 52. The movement ofswitch 45 disconnects integra tor 50 from line 42 and hence from thedensity input waveform and connects it to the output of level divider 22via line 52 so that integrator 50 thereafter integrates the constantlevelB until the switch 46 opens. When the waveform decays to level Cand circuit 30 responds with an output on line 40, this output on line40 is passed to switching circuit 47 which reacts by causing itscontrolled switch 46 to open, thus ending integration until therespective switches are reset automatically or manually in preparationfor another determination of the rate of blood flow. Thus, theintegrator 50 produces an output which is the same substantially as if apure density waveform undistorted by recirculation had been integrated.

The output of integrator 50 is passed to conventional divider circuit 52which divides the output by a factor Y and the output of the dividercircuit 52 is then passed to a multiplier 54 which multiplies the signalby a factor X. The factors X and Y are determined in accordance with theamount of indicator injected upstream of the heart so that the output ofmultiplier '54 represents the final flow rate according to the relationdiscussed above. The factor X is preferably variable as shown in FIG. 3in accordance with the amount of indicator injected. The electricaloutput of multiplier 54 is passed to a conventional display 56 so thatthe flow rate can be readily and quickly observed and the output ofmultiplier 54 may also be passed to any other suitable recorder ormachine as necessary or desirable for recording or otherwise utilizingthe electrical signals produced.

Reference is now made to FIG. 4 which shows another similar embodimentof the invention for processing a density waveform to derive the flowrate of blood or other liquid moving in a closed circulatory system. Theinput density waveform is first passed to a conventional amplifier 100which is equipped with a conventional gain control 102. The amplifiedoutput of amplifier 100 then deflects a meter 104 from its zeroposition. Meter 104 is used for calibrating the equipment. Calibrationis accomplished by first manually depressing switch 106, thus connectingthe source of voltage V to the meter 104 via resistor 1 10, so thatresistors 110 and 1 12 act as a voltage divider to apply a predeterminedvoltage to one side of the meter 104. Next a standard input is appliedto the amplifier 100, which is chosen so that when amplifier is properlyadjusted the output of amplifier 100 will be exactly equalto the voltagewhich appears at the other side of meter 104 via the depressed switch106. When these voltages are equal the meter M will deflect to zero andany deviation from zero can be corrected by properly adjusting the gaincontrol 102. Thus, the arrangement shown in FIG. 4 permits a simplecalibration of the arrangement by depressing switch 106 and applying astandard predetermined input signal to amplifier 100.

The output of the amplifier 100 is transmitted to a phase inverter 110and from the phase inverter 110 to a differential circuit 112. Theoutput of amplifier 100 is also passed to a level hold circuit 1 14which serves to compensate for zero line drift after calibration. Theoutput on level hold circuitry 114 is likewise applied to differentialamplifier 112. A switch 115 is also provided between the level holdcircuit 114 and the amplifier 100 and this switch is preferably manuallyopened when the computer is being calibrated as described above. Thus,circuitry 114 prevents undue drift of a signal from the desired presetlevel.

The output of the differential circuit 112 is applied to peak holdcircuit 116 which operates in the same fashion as the peak hold circuitdescribed above with regard to FIG. 3. The output of differentialamplifier 112 is also applied to a switching circuit 120, with itscontrolled switch 122 normally in the position shown to connect theinput signal to the peak hold circuit 116 to the integrator 126. Inembodiment of FIG. 4, integrator 126 is simply a conventionaloperational amplifi er 128 with a capacitance 130 connected in parallelwith it. As in the embodiment of FIG. 3, a normally closed switch 132connects the output of switch 120 to the integrator 126. Thus, theintegrator 128 integrates the density waveform as it rises to its peakand begins its exponential decline until it reaches the level B.

The output of peak hold circuit 116 is also passed to voltage dividers140 and 142 which divide the detected peak level by factors K, and Krespectively, to generate the levels B and C which correspond to theamplitude on the density curve at which the integration of the rectangleis to begin and the amplitude at which integration of the rectangle ofheight B and width 1 is to cease. The output of voltage divider 140 ispassed to a comparator circuit 146 which also receives the input to peakhold circuit 116 and produces an output signal on line 148 when theamplitudes of these two signals are substantially equal. Likewise, thecomparator circuit 150 receives the output of voltage divider 142together with the input to the peak hold circuit 116 and produces asuitable output signal on line 160 whenever these two inputs to circuit150 are substantially equal.

The output signal produced by circuit 146 on line 148 is applied tocontrol terminal 171 of switching circuit 120 to cause the switchingcircuit 120 to shift its controlled switch 122 from the illustratedposition into connection with line 164 Circuit 120 can be any of anumber of conventional devices which respond to an input signal byshifting a switch such as switch 122. The shifting of switch 122connects integrator 126 to the output of the voltage divider 144 througha circuit 168 so that that integrator 126 thereafter integrates thevalue B until a switch 132 opens. The output of thesignal comparatorcircuit 150 is passed to switching circuit 168 which in response opensits controlled switch 132 to end integration of the rectangularsimulation of the remainder of the exponential tail at the time that thelevel C of the density waveform is detected Circuit 168 can be anyconventional device which will open a controlled switch when a suitablesignal is applied to it.

Moreover, the switch 120 shown in FIG. 3 is provided with resistors 170and 172 so that when the switch shifts from its illustrated positioninto connection with line 164 that level B is, in effect, doubled ormultiplied by some other factor with respect to the input density signalbecause of the relative values of the resistors 170 and 172. Thismultiplication permits the level C to be set much higher on theexponential curve than otherwise and, as shown in FIG. 2 and explainedabove, this permits use of only the least, distorted portion of theexponential tail.

The output of the integrator 126 is passed to circuit 173 which performsa division of the factor Q by the output signal of integrator 126. Thefactor Q corresponds to the amount of indicator injected into the bloodstream. The output of circuit 173 is transmitted to an analog or digitalvolt meter 174 or other suitable display device. If desired, the finalsignal can be recorded or otherwise employed by a digital computer orother device. A switch 176 is further provided between the circuitry 173and 174 and this normally closed switch is opened when the comparatorcircuit 150 produces an output signal on line 160. The opening of switch176 ends integration and freezes the value in the digital volt meter174.

Further, the output of integrator circuit 126 is passed to an alarmcomparator circuit 180 which also receives the input from the peak holdcircuit 116. Circuit 180 continuously compares the output of the peakhold circuit 116 and the output of integrator 126 with the v. referencesignal and produces an alarm signal which is transmitted to a suitablealarm device 182 whenever any of these values achieves 10 v. saturationlevel. Preferably, the alarm device 182 includes a red or other coloredlight which warns the operator that a malfunction is taking place andcircuitry also blocks the outputs of comparator circuits 146 and 150upon detection of a malfunction. Thus, if the input density signal iswithin the proper range but for some reason the integration continuesbeyond the proper time and integrator 126 is driven to saturation, analarm signal results on an alarm device 182 to warn the operator.

Further, to prevent small error signals, which may appear as backgroundfrom being displayed incorrectly as a flow rate Go-On circuitry isprovided. Circuitry 190 receives the output from integrator 126 andcontinuously transmits appropriate signals to comparators 146 and 150which enable them to operate only when the output of integrator 126exceedsa substantial preset value. After each operation of the device,all of the switches and comparator circuits are reset and the aboveprocedure can then be repeated to determine flow rate from another inputdensity curve.

It should be apparent from the above discussion that the novel inventionof this application, while especially useful in determining the rate offlow of blood pumped by the heart, can also be used in other closedcirculatory systems for determining fiow rate of a fluid. Many changesand modifications in the embodiment of the invention discussed abovecan, of course, be made without departing from the scope of theinvention, and that scope is intended to be limited only by the scope ofthe appended claims.

What is claimed is:

1. Apparatus for determining the rate of flow of fluid in a closedcirculatory system whereby a detectable indicator is injected into thesystem at a first point and the density of the indicator is detected ata second point to generate an electrical waveform which rises to a peakvalue and decays thereafter substantially exponentially toward zerountil recirculated indicator distorts the exponential tail comprising:

means for receiving said waveform and producing an output levelsubstantially equal to said peak value after said waveform passes saidpeak value,

first means for dividing said output level by a given factor to producea first level,

second means for dividing said output level by a given factor to producea second level,

first means for comparing said waveform with said first level andproducing a first signal when the amplitude of said waveform during theexponential decay is substantially equal to said first level,

second means for comparing said waveform with said second level andproducing a second signal when the amplitude of said waveform during theexponential decay is substantially equal to said second level,

integrating means for receiving an input and producing a continuousintegral of said input in the form of a continuous electrical signal,and

means for transmitting said waveform to said integrating means so thatsaid integrating means integrates said waveform, including means fordisconnecting said integrating means from said waveform and connectingsaid integrating means to said first dividing means so that saidintegrating means thereafter integrates said first level when said firstcomparing means produces said first signal and means for disconnectingsaid integrating means from said first dividing means when said secondcomparing means produces said second signal.

2. Apparatus as in claim 1 wherein said disconnecting and connectingmeans includes switch means having a first position connecting saidwaveform to said integrating means and a second position connecting saidfirst dividing means to said integrating means and means connected tosaid first comparing means for shifting said switch means from saidfirst to said second position when said first signal is produced.

3. Apparatus as in claim 2 wherein said disconnecting means includessecond switch means connecting said first switch means to saidintegrating means, and having an open and closed position and meansconnected to said second comparing means for shifting said second switchmeans from said closed to said open position when said second signal isproduced.

4. Apparatus as in claim 1 including means for receiving said outputlevel and said peak value, for comparing said output level and said peakvalue with the preset constant value and generating a malfunction signalwhen said comparison indicates equivalence.

5'. Apparatus as in claim 1 including means connected to said outputlevel receiving and producing means for receiving said output level anddisabling said first and second comparing means when said output levelis less than a given preset value.

6. Apparatus as in claim 1 including means connected to said first levelproducing means for receiving said first level and multiplying it by agiven factor before said first level is integrated.

7. Apparatus as in claim 1 including means connected to said outputlevel receiving and producing means for dividing said output level intoa signal representing the amount of indicator injected so as to generatea signal indicating said rate of flow.

8. Apparatus as in claim 7 wherein said output dividing means includesmeans connected to said output level receiving and producing means formultiplying said output level by a first factor means for dividing saidoutput by a second factor and means for varying said second factor.

9. Apparatus as in claim 1 further including means for calibrating saidapparatus.

10. Apparatus as in claim 9 including means for receiving and amplifyingsaid waveform and wherein said calibrating means includes meter meansconnected to the output of said amplifying means, means for applying agiven voltage to said meter means so that when said amplifying meansreceives a given calibrating input signal said meter means will deflectto a given point, and means for adjusting the gain of said amplifyingmeans.

11. Apparatus as in claim 1 including means connected to said outputlevel receiving and producing means for using said output level todetermine said rate of flow and means for displaying said rate of flow.

12. Apparatus for determining the rate of flow of fluid in a closedcirculatory system whereby a detectable indicator is injected into thesystem at a first point and the density of the indicator is detected ata second point to generate an electrical waveform which rises to a peakvalue and decays thereafter substantially exponentially toward zerountil recirculated indicator-distorts the exponential tail comprising:

means for receiving said waveform and producing an output levelsubstantially equal to said peak value after said waveform passes saidpeak value,

first means for dividing said output level by a given factor to producea first level,

second means for dividing said output to produce a second level,

first means for comparing said waveform with said first level andproducing a first signal when the amplitude of said waveform during theexponential decay is substantially equal to said first level,

second means for comparing said waveform with said second level andproducing a second signal when the amplitude of said waveform during theexponential decay is substantially equal to said second level,

integrating means for receiving an input and producing a continuousintegral of said input in the form of a continuous electrical signal,

means for transmitting said waveform to said integrating means so thatsaid integrating means integrates said waveform,

means for disconnecting said integrating means from said waveform ansconnecting said integrating means to said first dividing means so thatsaid integrating means level by a given factor thereafter integratessaid first level when said first comparing means produces said firstsignal,

means for disconnecting said integrating means from said first dividingmeans when said second comparing means produces said second signal,

means for dividing said output into a signal representing the amount ofindicator injected so as to generate a signal indicating said rate offlow,

means for receiving said output and said peak value for comparing saidoutput and said peak value with the constant value for generating amalfunction signal when said comparison indicates a malfunction,

means for receiving said first level and multiplying it by a givenfactor before said first level is integrated, and means for calibratingsaid apparatus.

13. A method of determining the rate of flow of fluid in a closedcirculatory system whereby a detectable indicator is in jected into thesystem at a first point and the density of the indicator is detected ata second point to generate an electrical signal the waveform of whichrises to a peak value and decays thereafter substantially exponentiallytoward zero until recirculated indicator distorts the exponential tailcomprising:

receiving said waveform and producing an output level substantiallyequal to said peak value after said waveform passes said peak value,

dividing said output level by a given factor to produce a first level,

dividing said output level by a given factor to produce a second level,

comparing said waveform with said first level and producing a firstsignal when the amplitude of said waveform during the exponential decayis substantially equal to said first level,

comparing said waveform with said second level and producing a secondsignal when the amplitude of said waveform during the exponential decayis substantially equal to said second level,

integrating said waveform until said first signal is produced,

and

integrating said first level after'said first signal is produced anduntil said second signal is produced and terminating the integrationwhen said second signal is produced.

14. A method as in claim 13 including the steps of receiving theintegrated waveform and the integrated first level and said peak value,for comparing said integrated waveform and said integrated first leveland said peak value with the constant value and generating a malfunctionsignal when said comparison indicates equivalence,

15. A method as in claim 13 including the steps of receiving saidintegrated waveform and said integrated first level and preventingcomparing when said output level is less than a given preset value.

16. A method as in claim 13 including the steps of receiving said firstlevel and multiplying it by a given factor before said first level isintegrated.

17. A method as in claim 13 including the steps of dividing said outputlevel into a signal representing the amount of indicator injected so asto generate a signal indicating said rate of flow.

18. A method of determining the rate of flow of fluid in a closedcirculatory system comprising the steps of:

injecting a detectable indicator into the system at a first point,

detecting the density of the indicator at a second point to generate anelectrical waveform which rises to a peak value and decays thereaftersubstantially exponentially toward zero until recirculated indicatordistorts the exponential tail,

receiving said waveform and producing an output level substantiallyequal to said peak value after said waveform passes said peak value,

dividing said output level by a given factor to produce a first level,

lOl028 052l waveform during the exponential decay is substantially equalto said second level, integrating said waveform until said first signalis produced,

and

integrating sad first level after said first signal is produced anduntil said second signal is produced.

1. Apparatus for determining the rate of flow of fluid in a closedcirculatory system whereby a detectable indicator is injected into thesystem at a first point and the density of the indicator is detected ata second point to generate an electrical waveform which rises to a peakvalue and decays thereafter substantially exponentially toward zerountil recirCulated indicator distorts the exponential tail comprising:means for receiving said waveform and producing an output levelsubstantially equal to said peak value after said waveform passes saidpeak value, first means for dividing said output level by a given factorto produce a first level, second means for dividing said output level bya given factor to produce a second level, first means for comparing saidwaveform with said first level and producing a first signal when theamplitude of said waveform during the exponential decay is substantiallyequal to said first level, second means for comparing said waveform withsaid second level and producing a second signal when the amplitude ofsaid waveform during the exponential decay is substantially equal tosaid second level, integrating means for receiving an input andproducing a continuous integral of said input in the form of acontinuous electrical signal, and means for transmitting said waveformto said integrating means so that said integrating means integrates saidwaveform, including means for disconnecting said integrating means fromsaid waveform and connecting said integrating means to said firstdividing means so that said integrating means thereafter integrates saidfirst level when said first comparing means produces said first signaland means for disconnecting said integrating means from said firstdividing means when said second comparing means produces said secondsignal.
 2. Apparatus as in claim 1 wherein said disconnecting andconnecting means includes switch means having a first positionconnecting said waveform to said integrating means and a second positionconnecting said first dividing means to said integrating means and meansconnected to said first comparing means for shifting said switch meansfrom said first to said second position when said first signal isproduced.
 3. Apparatus as in claim 2 wherein said disconnecting meansincludes second switch means connecting said first switch means to saidintegrating means, and having an open and closed position and meansconnected to said second comparing means for shifting said second switchmeans from said closed to said open position when said second signal isproduced.
 4. Apparatus as in claim 1 including means for receiving saidoutput level and said peak value, for comparing said output level andsaid peak value with the preset constant value and generating amalfunction signal when said comparison indicates equivalence. 5.Apparatus as in claim 1 including means connected to said output levelreceiving and producing means for receiving said output level anddisabling said first and second comparing means when said output levelis less than a given preset value.
 6. Apparatus as in claim 1 includingmeans connected to said first level producing means for receiving saidfirst level and multiplying it by a given factor before said first levelis integrated.
 7. Apparatus as in claim 1 including means connected tosaid output level receiving and producing means for dividing said outputlevel into a signal representing the amount of indicator injected so asto generate a signal indicating said rate of flow.
 8. Apparatus as inclaim 7 wherein said output dividing means includes means connected tosaid output level receiving and producing means for multiplying saidoutput level by a first factor means for dividing said output by asecond factor and means for varying said second factor.
 9. Apparatus asin claim 1 further including means for calibrating said apparatus. 10.Apparatus as in claim 9 including means for receiving and amplifyingsaid waveform and wherein said calibrating means includes meter meansconnected to the output of said amplifying means, means for applying agiven voltage to said meter means so that when said amplifying meansreceives a given calibrating input signal said meter means will deflectto a given point, and means for adjusting the gain of said amplifyingmeans.
 11. Apparatus as in claim 1 including means connected to saidoutput level receiving and producing means for using said output levelto determine said rate of flow and means for displaying said rate offlow.
 12. Apparatus for determining the rate of flow of fluid in aclosed circulatory system whereby a detectable indicator is injectedinto the system at a first point and the density of the indicator isdetected at a second point to generate an electrical waveform whichrises to a peak value and decays thereafter substantially exponentiallytoward zero until recirculated indicator distorts the exponential tailcomprising: means for receiving said waveform and producing an outputlevel substantially equal to said peak value after said waveform passessaid peak value, first means for dividing said output level by a givenfactor to produce a first level, second means for dividing said outputlevel by a given factor to produce a second level, first means forcomparing said waveform with said first level and producing a firstsignal when the amplitude of said waveform during the exponential decayis substantially equal to said first level, second means for comparingsaid waveform with said second level and producing a second signal whenthe amplitude of said waveform during the exponential decay issubstantially equal to said second level, integrating means forreceiving an input and producing a continuous integral of said input inthe form of a continuous electrical signal, means for transmitting saidwaveform to said integrating means so that said integrating meansintegrates said waveform, means for disconnecting said integrating meansfrom said waveform ans connecting said integrating means to said firstdividing means so that said integrating means thereafter integrates saidfirst level when said first comparing means produces said first signal,means for disconnecting said integrating means from said first dividingmeans when said second comparing means produces said second signal,means for dividing said output into a signal representing the amount ofindicator injected so as to generate a signal indicating said rate offlow, means for receiving said output and said peak value for comparingsaid output and said peak value with the constant value for generating amalfunction signal when said comparison indicates a malfunction, meansfor receiving said first level and multiplying it by a given factorbefore said first level is integrated, and means for calibrating saidapparatus.
 13. A method of determining the rate of flow of fluid in aclosed circulatory system whereby a detectable indicator is injectedinto the system at a first point and the density of the indicator isdetected at a second point to generate an electrical signal the waveformof which rises to a peak value and decays thereafter substantiallyexponentially toward zero until recirculated indicator distorts theexponential tail comprising: receiving said waveform and producing anoutput level substantially equal to said peak value after said waveformpasses said peak value, dividing said output level by a given factor toproduce a first level, dividing said output level by a given factor toproduce a second level, comparing said waveform with said first leveland producing a first signal when the amplitude of said waveform duringthe exponential decay is substantially equal to said first level,comparing said waveform with said second level and producing a secondsignal when the amplitude of said waveform during the exponential decayis substantially equal to said second level, integrating said waveformuntil said first signal is produced, and integrating said first levelafter said first signal is produced and until said second signal isproduced and terminating the integration when said second signal isproduced.
 14. A method as in claim 13 including the steps of receivingthe integrated waveform and the integrated first level and said peakvalue, for comparing said integrated waveform and said integrated firstlevel and said peak value with the constant value and generating amalfunction signal when said comparison indicates equivalence.
 15. Amethod as in claim 13 including the steps of receiving said integratedwaveform and said integrated first level and preventing comparing whensaid output level is less than a given preset value.
 16. A method as inclaim 13 including the steps of receiving said first level andmultiplying it by a given factor before said first level is integrated.17. A method as in claim 13 including the steps of dividing said outputlevel into a signal representing the amount of indicator injected so asto generate a signal indicating said rate of flow.
 18. A method ofdetermining the rate of flow of fluid in a closed circulatory systemcomprising the steps of: injecting a detectable indicator into thesystem at a first point, detecting the density of the indicator at asecond point to generate an electrical waveform which rises to a peakvalue and decays thereafter substantially exponentially toward zerountil recirculated indicator distorts the exponential tail, receivingsaid waveform and producing an output level substantially equal to saidpeak value after said waveform passes said peak value, dividing saidoutput level by a given factor to produce a first level, dividing saidoutput level by a given factor to produce a second level, comparing saidwaveform with said first level and producing a first signal when theamplitude of said waveform during the exponential decay is substantiallyequal to said first level, comparing said waveform with said secondlevel and producing a second signal when the amplitude of said waveformduring the exponential decay is substantially equal to said secondlevel, integrating said waveform until said first signal is produced,and integrating sad first level after said first signal is produced anduntil said second signal is produced.